Tnk1 is a non-receptor protein tyrosine kinase with a putative size of 72 kDa, and is a member of ACK-tyrosine kinase family. It is related to the Ack1 (TNK2) non-receptor kinase that binds to cdc42 and inhibits its GTPase activity. The catalytic domain of TNK1 is located at the N terminus followed by a SH3 domain and a proline rich region. Tnk1 is expressed in core blood, bone marrow, and leukemia cell lines (see Hoehn et al, Oncogene. 12(4):903-13 (1996)). Tnk1 interacts with Phospholipase C gamma (PLC-g). It facilitates TNF alpha-induced apoptosis by blocking NF-kB activation (see Felschow et al., Biochem Biophys Res Commun 73(1):294-301 (2000); Azoieti et al., Oncogene. (2007) 26:6536-6545). Active TNK1 may play a role in regulating cell death by preventing TNF-a induced NF-kB transactivation (Azoieti et al., Oncogene. (2007) 26:6536-6545).
Tnk1/Kos1 is a tumor suppressor in both human and mouse. Loss of Tnk1/kos1 in mice results in the spontaneous development of tumors namely diffuse large B-cell lymphomas (DLBCL), hepatocellular carcinomas, adenocarcinomas of lung, etc. Apart from the loss of human Tnk1 protein in a cohort of patients with DLBCL, the inventors have now realized that over expression of a 60 kDa truncated Tnk1 fusion gene product has been found in a patient with Hodgkin Lymphoma and in other cancers. The truncated Tnk1 protein though tyrosine phosphorylated is oncogenic because it is kinase dead and associated with increased Ras-MAPK activities. To date, effective Tnk1-Kos1 antibodies are not commercially available.